One possibility for the effective prevention of breast cancer lies in a better understanding of different physiological conditions which show tumor-inhibiting capabilities, including morphological changes in the mammary gland gland and a number of biochemical and hormonal determinants which can be modulated by diet. Both human and animal data suggest that a relationship exists between nutrition and the incidence of cancer. Experiments using rodents as models have shown that measured caloric restriction throughout the postweaning developmental stage markedly reduces the incidence of many diseases, particularly the occurrence and growth of tumors. However, despite the significant research that has been done on dietary restriction and its effects on specific tumor-controlling mechanisms, few studies have attempted to relate quantified levels of dietary limitation with mammary tumor incidence and data from such studies would enable us to identify if there is a "critical" level of restriction that is necessary to achieve a tumor-inhibiting effect. Further studies are also needed in order to elaborate the biochemical, endocrinological and morphological changes affecting breast cancer induction, which accompany a systematic restriction of normal diet. The research proposed in this application is therefore intended to identify if there is a "critical" levels of dietary restriction or perhaps a "critical" period during which caloric restriction is most effective in achieving tumor inhibition and to elucidate the mechanisms by which dietary restriction achieves its known tumor-inhibiting effect. The studies will be carried out using induced and spontaneous tumorigenesis and tumor growth in female laboratory rats, and it is hoped that the data from these studies will lead to the formulation of scientifically based dietary guidelines for the reduction of cancer risk in humans.